Association between Postmenopausal Osteoporosis and IL-6、TNF-α: A Systematic Review and A Meta-analysis.

BACKGROUND: Postmenopausal osteoporosis (PMOP) greatly increases the risk of bone fracture in postmenopausal women, seriously affects the quality of life of patients, and is an important global public health problem. Persistent chronic systemic inflammation may be involved in the change process of PMOP, and many cytokines, such as TNF-alpha and Interleukin-6, play an important role in the inflammatory response. Therefore, This study takes commonly representative inflammatory factors as indicators to better determine their role in PMOP patients by means of databases from multiple studies for use in Meta-analysis. METHOD: Systematic review of studies on the relationship between PMOP and markers of inflammation: interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). Each effect size was expressed with a 95% confidence interval (CI), and I2 quantified the heterogeneity. The final results were aggregated and evaluated using random or fixed effects models. RESULTS: Twenty-one original studies were identified. There were twenty studies involving IL-6 and eleven involving TNF-α. Overall, The levels of IL-6[MD=23.93, 95%CI (19.65, 28.21)] and TNF-α[MD=2.9, 95%CI (2.37, 3.44)] were increased in PMOP patients compared with postmenopausal women without osteoporosis; The levels of IL-6[MD=42.4, 95%CI (38.62, 46.19)] and TNF-α[MD=0.40, 95%CI (0.36, 0.44)] were significantly higher than those of premenopausal healthy women. CONCLUSIONS: The levels of inflammatory cytokines IL-6 and TNF-α were significantly increased in PMOP patients compared with controls, suggesting that persistent chronic inflammatory reaction exists in PMOP patients, which may be an important cause of aggravated osteoporosis in postmenopausal women. Therefore, the level of IL-6 and TNF-α indexes may be of great significance for the early prevention, diagnosis, treatment and prognosis assessment of PMOP.

Loganin reduces neuroinflammation and promotes functional recovery after spinal cord injury through inhibiting NF-κB/NLRP3 signalling.

The highly disabling nature of spinal cord injuries (SCI) and high cost of treatment and rehabilitation impose a burden on families and society. Loganin has potential medicinal value in alleviating neuroinflammation. This study aimed to explore whether loganin can be used to reduce SCI-induced neuroinflammation and elucidate the molecular mechanisms underlying its action. An SCI rat model was developed to assess whether loganin promotes motor recovery after SCI. The anti-inflammatory effects of loganin on the dorsal horn of the spinal cord were identified by haematoxylin-eosin and immunohistochemical staining. The inflammatory effects of loganin were characterised using a lipopolysaccharide (LPS)-induced neuroinflammatory model in BV2 cells. For mechanistic exploration, the signalling pathways and target proteins of loganin action were predicted using bioinformatics and computational biology and then validated in cellular inflammation models. Loganin promoted animal motor recovery after SCI at the behavioural level, and it inhibited M1 differentiation of microglia and reduced NOD-like receptor thermal protein domain associated protein 3 (NLRP3)-mediated inflammatory responses at the tissue level. Loganin inhibited LPS-induced inflammation in BV2 cells, and bioinformatics and computational biology suggested that loganin acts on the p65 protein through the nuclear factor kappa-B (NF-κB)/NLRP3 signalling pathway. This was validated in a cellular model in which p65 trans-overexpression eliminated the downregulation of inflammatory factors by loganin. In conclusion, loganin reduces neuroinflammatory responses and promotes motor recovery after SCI. Loganin inhibits the NF-κB/NLRP3 signalling pathway by targeting the p65 protein to achieve repair.

Network Pharmacological Study on Mechanism of the Therapeutic Effect of Modified Duhuo Jisheng Decoction in Osteoporosis.

Background: Modified Duhuo Jisheng Decoction (MDHJSD) is a traditional Chinese medicine prescription for the treatment of osteoporosis (OP), but its mechanism of action has not yet been clarified. This study aims to explore the mechanism of MDHJSD in OP through a combination of network pharmacology analysis and experimental verification. Methods: The active ingredients and corresponding targets of MDHJSD were acquired from the Traditional Chinese Medicine System Pharmacology (TCMSP) database. OP-related targets were acquired from databases, including Genecards, OMIM, Drugbank, CTD, and PGKB. The key compounds, core targets, major biological processes, and signaling pathways of MDHJSD that improve OP were identified by constructing and analysing the relevant networks. The binding affinities between key compounds and core targets were verified using AutoDock Vina software. A rat model of ovariectomized OP was used for the experimental verification. Results: A total of 100 chemical constituents, 277 targets, and 4734 OP-related targets of MDHJSD were obtained. Subsequently, five core components and eight core targets were identified in the analysis. Pathway enrichment analysis revealed that overlapping targets were significantly enriched in the tumour necrosis factor-alpha (TNF-α) signaling pathway, an inflammation signaling pathway, which contained six of the eight core targets, including TNF-α, interleukin 6 (IL-6), transcription factor AP-1, mitogen-activated protein kinase 3, RAC-alpha serine/threonine-protein kinase, and caspase-3 (CASP3). Molecular docking analysis revealed close binding of the six core targets of the TNF signaling pathway to the core components. The results of experimental study show that MDHJSD can protect bone loss, inhibit the inflammatory response, and downregulate the expression levels of TNF-α, IL-6, and CASP3 in ovariectomized rats. Conclusion: The mechanism of MDHJSD in the treatment of OP may be related to the regulation of the inflammatory response in the bone tissue.